A genetic and biochemical approach is planned to identify chain- termination mutations and suppressor tRNAs in animal cells and chain termination mutations in animal viruses. These genetic tools would provide an effective new method for the analysis of oncogenic viruses and to study the molecular basis of cancer. A cloned chinese hamster cell line will be used initially although the studies will eventually be extended to include mouse, monkey, and human cell lines. A suppressor can be genetically identified as a mutation which produces the concurrent reversion of mutations at two distinct loci. Mutations in genes for glutamine synthetase, hypoxanthine-guanine phosphoribosyl transferase, thymidine kinase, and purine nucleoside phosphorylase will be examined. These gene products will be purified and characterized. Herpes simplex virus type -1 (HSV) will be used for animal virus studies. Mutants in the non-essential virus thymidine kinase gene will be analyzed for chain termination. In addition, cells transformed by HSV will be used as permissive hosts for the growth of potential HSV chain termination mutants. Chain-termination mutations will be identified by examining mutated gene products on sodium dodecyl sulfates polyacrylamide gels.